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7_lymphocyte_receptor_signaling.md

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Lymphocyte Receptor Signaling

General principals of signal transduction and propogation

Multiprotein signaling complexes

Composition of multiple proteins is crucial for proper downstream signal propogation.

SH2

  • YXXZ

Scaffolds Adapters

Small G Proteins are molecular switches

Also called small GTPase

Include:

  • Ras
  • Rho
  • Rac

Have two states - bound to GDP or GTP.

Role of following in "swtiching" G proteins:

  • Guanine Nucleotide Exchange Factors (GNEFs)
  • GTPase Activating Proteins (GAPs) are cofactors that

Mostly found in their inactive (GDP-bound) state

Localized to membrane by fatty acids attached post translationally

Signaling proteins are recruited to the membrane in different ways

  1. Phosphorylation of receptor itself or scaffold, followed by recognition by SH2-domain containing signaling proteins or adaptors
  2. Binding to small GTPases already bound to membrane by attached lipids
  3. Recognition of locally phosphorylated membrane lipids

phospholipid phosphatidylinositol are phosphorylated by enzymes called phosphatidylinositol kinases to produce PIP_2 and PIP_3 (2 and 3 phosphates on carbon rings). These enzymes are recruited by its SH2 domain to phosphotyrosine on the tail of some receptor.

Post translational protein modification can effect signal response

Phophate and ubiquitin additions to proteins can modulate constituents of signal cascades.

Ubiquitin ligases (like Cbl) can be recruited by SH2 domains, so tyrosine-phosphorylated targets can be modified by additional ubiquitin and then targeted to degradation pathways.

Antigen receptor signaling in lymphocytes

Antigen binding is not enough - signal needs to transduce to intracellular components...

CD3 + ITAMs

Immunoreceptor Tyrosine-based Activation Motifs